Marjolein de Wit, M.D., Assistant Professor of Medicine in the Pulmonary and Critical Care Division at Virginia Commonwealth University, seeks support for this research training in order to establish herself as an independent clinical investigator examining sedation of critically ill patient. Her goal is to evaluate the effectiveness of various sedation strategies, to evaluate the prevalence of psychiatric complications, and to compute the pharmacokinetics of commonly used sedatives. In order to enhance her research skills, Dr. de Wit will enroll in a master's degree program in clinical research and design offered by the institution as well as obtain formal training in pharmacokinetics and pharmacodynamics. Certain methods of sedation increase the duration of respiratory failure. Two strategies, a nursing-implemented sedation algorithm and daily interruption of sedatives, decrease length of mechanical ventilation compared to "conventional care" but have not been compared to each other. The reason certain methods of sedation lead to prolonged respiratory failure is unknown but may be related to altered pharmacokinetics and dynamics that are unique to critically ill patients. Critically ill patients receive substantial doses of sedatives over prolonged periods. The impact of these management strategies on short- and long-term psychiatric complications are unknown. The study proposed in this grant application seeks to test the central hypothesis that sedation practices impact strongly on outcome of respiratory failure and psychiatric complications. The three specific aims are (1) to compare two sedation strategies (protocol directed sedation and daily interruption of sedatives), (2) to examine the prevalence of psychiatric complications, and (3) to compute the pharmacokinetics of commonly used sedatives and narcotics. These aims will be achieved by enrolling critically ill patients in a prospective randomized trial comparing the above mentioned sedation strategies, and assessing sedation level as well as delirium throughout the duration of respiratory failure. Sedative plasma levels will be measured, and pharmacokinetics computed. Psychiatric morbidity will be assessed by administration of validated questionnaires. This study design creates a pathway for new understanding of the impact of sedation and the incidence of morbidity.